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1. Fundamentals of the Nervous System and Nervous Tissue: Part B 11

2. Neurons are highly irritable Respond to adequate stimulus by generating an action potential (nerve impulse) Impulse is always the same regardless of stimulus Neuron Function

3. Opposite charges attract each other Energy is required to separate opposite charges across a membrane Energy is liberated when the charges move toward one another If opposite charges are separated, the system has potential energy Principles of Electricity

4. Voltage (V): measure of potential energy generated by separated charge Potential difference: voltage measured between two points Current (I): the flow of electrical charge (ions) between two points Definitions

5. Resistance (R): hindrance to charge flow (provided by the plasma membrane) Insulator: substance with high electrical resistance Conductor: substance with low electrical resistance Definitions

6. Proteins serve as membrane ion channels • Two main types of ion channels • Leakage (nongated) channels—always open Role of Membrane Ion Channels

7. Gated channels (three types): • Chemically gated (ligand-gated) channels—open with binding of a specific neurotransmitter • Voltage-gated channels—open and close in response to changes in membrane potential • Mechanically gated channels—open and close in response to physical deformation of receptors Role of Membrane Ion Channels

8. Receptor Neurotransmitter chemical attached to receptor Na+ Na+ Na+ Na+ Chemical binds Membrane voltage changes K+ K+ Closed Open Closed Open (a) Chemically (ligand) gated ion channels open when theappropriate neurotransmitter binds to the receptor,allowing (in this case) simultaneous movement of Na+ and K+. (b) Voltage-gated ion channels open and close in responseto changes in membrane voltage. Figure 11.6

9. When gated channels are open: • Ions diffuse quickly across the membrane along their electrochemical gradients • Along chemical concentration gradients from higher concentration to lower concentration • Along electrical gradients toward opposite electrical charge • Ion flow creates an electrical current and voltage changes across the membrane Gated Channels

10. Potential difference across the membrane of a resting cell • Approximately –70 mV in neurons (cytoplasmic side of membrane is negatively charged relative to outside) • Generated by: • Differences in ionic makeup of ICF and ECF • Differential permeability of the plasma membrane Resting Membrane Potential (Vr)

11. Voltmeter Plasma membrane Ground electrode outside cell Microelectrode inside cell Axon Neuron Figure 11.7

12. Differences in ionic makeup • ICF has lower concentration of Na+ and Cl– than ECF • ICF has higher concentration of K+ and negatively charged proteins (A–) than ECF Resting Membrane Potential

13. Differential permeability of membrane • Impermeable to A– • Slightly permeable to Na+ (through leakage channels) • 75 times more permeable to K+ (more leakage channels) • Freely permeable to Cl– Resting Membrane Potential

14. Negative interior of the cell is due to much greater diffusion of K+ out of the cell than Na+ diffusion into the cell Sodium-potassium pump stabilizes the resting membrane potential by maintaining the concentration gradients for Na+ and K+ Resting Membrane Potential

15. The concentrations of Na+ and K+ on each side of the membrane are different. Outside cell The Na+ concentration is higher outside the cell. Na+ (140 mM) K+ (5 mM) The K+ concentration is higher inside the cell. K+ (140 mM) Na+ (15 mM) Na+-K+ ATPases (pumps) maintain the concentration gradients of Na+ and K+ across the membrane. Inside cell The permeabilities of Na+ and K+ across the membrane are different. Suppose a cell has only K+ channels... K+ loss through abundant leakage channels establishes a negative membrane potential. K+ leakage channels K+ K+ Cell interior –90 mV K+ K+ Now, let’s add some Na+ channels to our cell... Na+ entry through leakage channels reduces the negative membrane potential slightly. K+ K+ Na+ Cell interior –70 mV K K+ Na+ Finally, let’s add a pump to compensate for leaking ions. Na+-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential. Na+-K+ pump K+ K+ Na+ K+ K+ Cell interior –70 mV Na+ Figure 11.8

16. Membrane potential changes when: • Concentrations of ions across the membrane change • Permeability of membrane to ions changes • Changes in membrane potential are signals used to receive, integrate and send information Membrane Potentials That Act as Signals

17. Two types of signals • Graded potentials • Incoming short-distance signals • Action potentials • Long-distance signals of axons Membrane Potentials That Act as Signals

18. Depolarization • A reduction in membrane potential (toward zero) • Inside of the membrane becomes less negative than the resting potential • Increases the probability of producing a nerve impulse Changes in Membrane Potential

19. Depolarizing stimulus Inside positive Inside negative Depolarization Resting potential Time (ms) (a) Depolarization: The membrane potentialmoves toward 0 mV, the inside becoming less negative (more positive). Figure 11.9a

20. Hyperpolarization • An increase in membrane potential (away from zero) • Inside of the membrane becomes more negative than the resting potential • Reduces the probability of producing a nerve impulse Changes in Membrane Potential

21. Hyperpolarizing stimulus Resting potential Hyper- polarization Time (ms) (b) Hyperpolarization: The membranepotential increases, the inside becomingmore negative. Figure 11.9b

22. Short-lived, localized changes in membrane potential Depolarizations or hyperpolarizations Graded potential spreads as local currents change the membrane potential of adjacent regions Graded Potentials

23. Stimulus Depolarized region Plasma membrane (a) Depolarization: A small patch of the membrane (red area) has become depolarized. Figure 11.10a

24. (b) Spread of depolarization: The local currents (black arrows) that are created depolarize adjacent membrane areas and allow the wave of depolarization to spread. Figure 11.10b

25. Occur when a stimulus causes gated ion channels to open • E.g., receptor potentials, generator potentials, postsynaptic potentials • Magnitude varies directly (graded) with stimulus strength • Decrease in magnitude with distance as ions flow and diffuse through leakage channels • Short-distance signals Graded Potentials

26. Active area (site of initial depolarization) Membrane potential (mV) –70 Resting potential Distance (a few mm) (c) Decay of membrane potential with distance: Because current is lost through the “leaky” plasma membrane, the voltage declines with distance from the stimulus (the voltage is decremental). Consequently, graded potentials are short-distance signals. Figure 11.10c

27. Brief reversal of membrane potential with a total amplitude of ~100 mV Occurs in muscle cells and axons of neurons Does not decrease in magnitude over distance Principal means of long-distance neural communication Action Potential (AP)

28. The big picture 1 3 2 Resting state Depolarization Repolarization 3 4 Hyperpolarization Membrane potential (mV) Action potential 2 Threshold 1 1 4 Time (ms) Figure 11.11 (1 of 5)

29. Resting state • Only leakage channels for Na+ and K+ are open • All gated Na+ and K+ channels are closed Generation of an Action Potential

30. Properties of gated channels • Each Na+ channel has two voltage-sensitive gates • Activation gates • Closed at rest; open with depolarization • Inactivation gates • Open at rest; block channel once it is open Properties of Gated Channels

31. Each K+ channel has one voltage-sensitive gate Closed at rest Opens slowly with depolarization Properties of Gated Channels

32. Depolarizing local currents open voltage-gated Na+ channels Na+ influx causes more depolarization At threshold (–55 to –50 mV) positive feedback leads to opening of all Na+ channels, and a reversal of membrane polarity to +30mV (spike of action potential) Depolarizing Phase

33. Repolarizing phase • Na+ channel slow inactivation gates close • Membrane permeability to Na+ declines to resting levels • Slow voltage-sensitive K+ gates open • K+ exits the cell and internal negativity is restored Repolarizing Phase

34. Hyperpolarization • Some K+ channels remain open, allowing excessive K+ efflux • This causes after-hyperpolarization of the membrane (undershoot) Hyperpolarization

35. The AP is caused by permeability changes in the plasma membrane 3 Action potential Membrane potential (mV) Na+ permeability Relative membrane permeability 2 K+ permeability 1 1 4 Time (ms) Figure 11.11 (2 of 5)

36. Repolarization • Restores the resting electrical conditions of the neuron • Does not restore the resting ionic conditions • Ionic redistribution back to resting conditions is restored by the thousands of sodium-potassium pumps Role of the Sodium-Potassium Pump

37. Na+ influx causes a patch of the axonal membrane to depolarize Local currents occur Na+ channels toward the point of origin are inactivated and not affected by the local currents Propagation of an Action Potential

38. Local currents affect adjacent areas in the forward direction Depolarization opens voltage-gated channels and triggers an AP Repolarization wave follows the depolarization wave (Fig. 11.12 shows the propagation process in unmyelinated axons.) Propagation of an Action Potential

39. Voltage at 0 ms Recording electrode (a) Time = 0 ms. Action potential has not yet reached the recording electrode. Resting potential Peak of action potential Hyperpolarization Figure 11.12a

40. Voltage at 2 ms (b) Time = 2 ms. Action potential peak is at the recording electrode. Figure 11.12b

41. Voltage at 4 ms (c) Time = 4 ms. Action potential peak is past the recording electrode. Membrane at the recording electrode is still hyperpolarized. Figure 11.12c

42. At threshold: • Membrane is depolarized by 15 to 20 mV • Na+ permeability increases • Na influx exceeds K+ efflux • The positive feedback cycle begins Threshold

43. Subthreshold stimulus—weak local depolarization that does not reach threshold Threshold stimulus—strong enough to push the membrane potential toward and beyond threshold AP is an all-or-none phenomenon—action potentials either happen completely, or not at all Threshold

44. All action potentials are alike and are independent of stimulus intensity • How does the CNS tell the difference between a weak stimulus and a strong one? • Strong stimuli can generate action potentials more often than weaker stimuli • The CNS determines stimulus intensity by the frequency of impulses Coding for Stimulus Intensity

45. Action potentials Stimulus Threshold Time (ms) Figure 11.13

46. Time from the opening of the Na+ channels until the resetting of the channels Ensures that each AP is an all-or-none event Enforces one-way transmission of nerve impulses Absolute Refractory Period

47. Absolute refractory period Relative refractory period Depolarization (Na+ enters) Repolarization (K+ leaves) After-hyperpolarization Stimulus Time (ms) Figure 11.14

48. Follows the absolute refractory period • Most Na+ channels have returned to their resting state • Some K+ channels are still open • Repolarization is occurring • Threshold for AP generation is elevated • Exceptionally strong stimulus may generate an AP Relative Refractory Period

49. Conduction velocities of neurons vary widely • Effect of axon diameter • Larger diameter fibers have less resistance to local current flow and have faster impulse conduction • Effect of myelination • Continuous conduction in unmyelinated axons is slower than saltatory conduction in myelinated axons Conduction Velocity

50. Effects of myelination • Myelin sheaths insulate and prevent leakage of charge • Saltatory conduction in myelinated axons is about 30 times faster • Voltage-gated Na+ channels are located at the nodes • APs appear to jump rapidly from node to node Conduction Velocity